A Phase I/II multicenter study of IY5511HCl in Philadelphia chromosome positive chronic myeloid leukemia patients without optimal response or tolerance to Bcr-Abl tyrosine kinase inhibitors (Imatinib and/ or Dasatinib, Nilotinib) In this study, The efficacy and safety of CML patients who are resistant or intolerable to imatinib in the Chronic and Accelerated phases.

Phase 1

1. To investigate the Maximum Tolerated Dose (MTD) and the Dose Limiting Toxicity (DLT) of oral Radotinib HCl bid (twice daily) in the Philadelphia chromosome-positive CML subjects who are resistant, suboptimal responsive, or intolerant to imatinib OR resistant or intolerant to at least one second-generation targeted anticancer agent while being resistant, suboptimal responsive, or intolerant to imatinib simultaneously.

Phase 2

To investigate safety of oral Radotinib HCl in CML patients who are resistant or intolerable to imatinib in the chronic and accelerated phases.

To evaluate hematologic and cytogenetic efficacy of oral Radotinib HCl in CML patients who are resistant or intolerable to imatinib in the chronic and accelerated phases.

Main parameters for response assessment in the chronic and accelerated phases include Major Hematologic Responses (MR; No Evidence of Leukemia or NEL + Complete Hematologic Response or CHR) lasting for 4 weeks and at least one major cytogenetic response (MCyR)

It is defined as the duration from the first day of administration to the earliest day of disease progression or death for certain causes. In subjects who have shown response, disease progression is defined as loss of MCyR.

This study is a multi-center, open-label, Phase 1/2 clinical trial of Radotinib HCl, a targeted anticancer agent that inhibits the Bcr-Abl oncoprotein. It is aimed at determining the optimal therapeutic dose and confirming safety and efficacy of Radotinib HCl. Phase 1 study began at St. Mary's hospital in Korea and Phase 2 study is ongoing at 9 Korean sites and about 7 sites in China, India and Thailand will take part in Phase 2. After determination of a safe and proper therapeutic dose in Phase 1, Phase 2 began continuously to evaluate efficacy in chronic and accelerated phases. Before the start of the Phase 2 trial, interim or final reports for the Phase 1 trial were reviewed by the Korean Food and Drug Administration.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Phase I

Age ≥ 18 years old

Ph+ CML patients who are resistant at chronic, accelerate, and acute phase, or suboptimal responsive, or intolerant to imatinib or resistant or intolerant to at least one second-generation targeted anticancer agent while being resistant, suboptimal responsive, or intolerant to imatinib simultaneously.

WHO Performance status of ≤2

Patients must have the following laboratory values With normal liver and renal function

Patients who have received interferon, other anti cancer drug or radiotherapy > 1 week prior to starting study drug.

Phase II

Age ≥ 18 years old

Ph+ CML patients in chronic or accelerated phase who are resistant or intolerant to Imatinib mesylate

WHO Performance status of ≤2

Patients must have the following laboratory values With normal liver and renal function

Patients who have received interferon, other anti cancer drug or radiotherapy > 1 week prior to starting study drug.

Patients who are currently receiving treatment with medications have the potential to prolong the QT interval

Patients who have received Imatinib, interferon, other anti cancer drug or chemotherapy ≤ 1 week

Patients who have received wide field radiotherapy ≤4 weeks prior to starting study drug.

Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

Patients who are pregnant or breast-feeding or adults of reproductive potential not employing an effective method of birth control

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01602952